ArticleThe EMBO journal2018
Thermal proteome profiling of breast cancer cells reveals proteasomal activation by CDK4/6 inhibitor palbociclib.
Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 106 citations in OpenAlex.
- DORSSAA: Drug-Target interactOmics Resource Based on Stability/Solubility Alteration Assay.Molecular & cellular proteomics : MCP · 2026Article
- Molecular mechanisms underlying liposarcoma subtype transition and proteasome-associated targeted interventions.Journal of translational medicine · 2026Review
- Charting the multilevel molecular response to palbociclib in ER-positive breast cancer.NAR cancer · 2026Article
- Co-targeting CDK4/6 enhances anti-cancer activity and alleviates immune-related adverse events of anti-PD-1 antibody for breast cancer.Cell reports. Medicine · 2025Article
- Top-Down Thermal Proteome Profiling (TD-TPP) for Functional Characterization of the Intact Proteoforms in Complex Samples.Journal of mass spectrometry : JMS · 2025Article
- Suppressing protein damage response to overcome multidrug resistance in cancer therapy.Cell discovery · 2025Article
- Article
- Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus MScience advances · 2025Article
- Article
- CDK4/6 inhibition initiates cell cycle arrest by nuclear translocation of RB and induces a multistep molecular response.Cell death discovery · 2024Article
- Whole-exome sequencing identifies ECPAS as a novel potentially pathogenic gene in multiple hereditary families with nonsyndromic orofacial cleft.Protein & cell · 2024Article
- Ethaverine and Papaverine Target Cyclin-Dependent Kinase 5 and Inhibit Lung Cancer Cell Proliferation and Migration.ACS pharmacology & translational science · 2024Article
- Mesenchymal stromal/stem cells promote intestinal epithelium regeneration after chemotherapy-induced damage.Stem cell research & therapy · 2024Article
- Experimental and data analysis advances in thermal proteome profiling.Cell reports methods · 2024Review
- Stability-Based Proteomics for Investigation of Structured RNA-Protein Interactions.Analytical chemistry · 2024Article
- Non-canonical pathway for Rb inactivation and external signaling coordinate cell-cycle entry without CDK4/6 activity.Nature communications · 2023Article
- Comparison of Quantitative Mass Spectrometric Methods for Drug Target Identification by Thermal Proteome Profiling.Journal of proteome research · 2023Article
- Firing of Replication Origins Is Disturbed by a CDK4/6 Inhibitor in a pRb-Independent Manner.International journal of molecular sciences · 2023Article
- BRD9 Degradation Disrupts Ribosome Biogenesis in Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Comparative Analysis of Protein Folding Stability-Based Profiling Methods for Characterization of Biological Phenotypes.Journal of the American Society for Mass Spectrometry · 2023Article
Corrections and comments
- Commented on by
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Palbociclib is a CDK4/6 inhibitor approved for metastatic estrogen receptor-positive breast cancer. In addition to G1 cell cycle arrest, palbociclib treatment results in cell senescence, a phenotype that is not readily explained by CDK4/6 inhibition. In order to identify a molecular mechanism responsible for palbociclib-induced senescence, we performed thermal proteome profiling of MCF7 breast cancer cells. In addition to affecting known CDK4/6 targets, palbociclib induces a thermal stabilization of the 20S proteasome, despite not directly binding to it. We further show that palbociclib treatment increases proteasome activity independently of the ubiquitin pathway. This leads to cellular senescence, which can be counteracted by proteasome inhibitors. Palbociclib-induced proteasome activation and senescence is mediated by reduced proteasomal association of ECM29. Loss of ECM29 activates the proteasome, blocks cell proliferation, and induces a senescence-like phenotype. Finally, we find that ECM29 mRNA levels are predictive of relapse-free survival in breast cancer patients treated with endocrine therapy. In conclusion, thermal proteome profiling identifies the proteasome and ECM29 protein as mediators of palbociclib activity in breast cancer cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.